Gene Therapy for Metastatic Castration-Resistant Prostate Cancer Using the JC Polyomavirus (JCPyV) Virus-Like Particles as a Gene Delivery Vector.
7 affiliations
- 1Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan.
- 2Department of Anatomic Pathology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.
- 3Department of Pharmacy, Chiayi Chang Gung Memorial Hospital, Puzi, Taiwan.
- 4Department of Microbiology and Immunology, School of Medicine, Chung-Shan Medical University and Clinical Laboratory, Chung-Shan Medical University Hospital, Taichung, Taiwan.
- 5Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
- 6Department of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
- 7Department of Medical Research, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
Abstract
Background
Systemic metastasis remains the leading cause of mortality in patients with advanced prostate cancer, particularly in castration-resistant prostate cancer (CRPC), for which effective systemic therapeutic options are limited. Gene therapy is a potential strategy for achieving selective tumor targeting and systemic disease control in metastatic settings. This study aimed to establish a systemic metastasis animal model for CRPC and evaluate the therapeutic efficacy of JC polyomavirus (JCPyV) virus-like particle (VLPs)-based gene therapy against metastatic disease.Methods
A near-infrared fluorescent protein (iRFP)-expressing CRPC cell line was used to establish a systemic metastasis model by tail-vein injection in mice. The therapeutic efficacy of JCPyV VLPs carrying a prostate-specific antigen (PSA) promoter-driven suicide gene (PSAtk-VLPs), administered in combination with ganciclovir (GCV), was evaluated longitudinally by fluorescence molecular tomography (FMT), with enzalutamide/leuprorelin acetate (ENZ/LEU) included as a clinical treatment comparator.Results
CRPC metastases in the lungs, liver, spleen, kidneys, and bones were detected by FMT in real time. Control mice exhibited exponential CRPC growth, whereas ENZ/LEU treatment delayed CRPC progression. PSAtk-VLPs/GCV significantly inhibited the growth of metastatic CRPC. However, no significant differences in survival were observed among the MOCK, ENZ/LEU, and PSAtk-VLP/GCV groups (log-rank test, p = 0.7351).Conclusion
These findings support that JCPyV-derived virus-like particles constitute a promising therapeutic approach for metastatic CRPC, enabling systemic delivery of suicide gene therapy with selective inhibition of tumor growth and translational relevance.
Related
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BibTeX
@article{chou2026gene,
title = {{Gene Therapy for Metastatic Castration-Resistant Prostate Cancer Using the JC Polyomavirus (JCPyV) Virus-Like Particles as a Gene Delivery Vector.}},
author = {Chih-Chieh Chou and Chih-En Tseng and Yu-Shih Lin and Meilin Wang and Pei-Lain Chen and Deching Chang and Cheng-Huang Shen and Chiung-Yao Fang},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72365},
url = {https://europepmc.org/article/MED/42897111},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Gene Therapy for Metastatic Castration-Resistant Prostate Cancer Using the JC Polyomavirus (JCPyV) Virus-Like Particles as a Gene Delivery Vector.
AU - Chih-Chieh Chou
AU - Chih-En Tseng
AU - Yu-Shih Lin
AU - Meilin Wang
AU - Pei-Lain Chen
AU - Deching Chang
AU - Cheng-Huang Shen
AU - Chiung-Yao Fang
PY - 2026
DA - 2026/10/01
JO - Cancer medicine
DO - 10.1002/cam4.72365
UR - https://europepmc.org/article/MED/42897111
AB - Background Systemic metastasis remains the leading cause of mortality in patients with advanced prostate cancer, particularly in castration-resistant prostate cancer (CRPC), for which effective systemic therapeutic options are limited. Gene therapy is a potential strategy for achieving selective tumor targeting and systemic disease control in metastatic settings. This study aimed to establish a systemic metastasis animal model for CRPC and evaluate the therapeutic efficacy of JC polyomavirus (JCPyV) virus-like particle (VLPs)-based gene therapy against metastatic disease.Methods A near-infrared fluorescent protein (iRFP)-expressing CRPC cell line was used to establish a systemic metastasis model by tail-vein injection in mice. The therapeutic efficacy of JCPyV VLPs carrying a prostate-specific antigen (PSA) promoter-driven suicide gene (PSAtk-VLPs), administered in combination with ganciclovir (GCV), was evaluated longitudinally by fluorescence molecular tomography (FMT), with enzalutamide/leuprorelin acetate (ENZ/LEU) included as a clinical treatment comparator.Results CRPC metastases in the lungs, liver, spleen, kidneys, and bones were detected by FMT in real time. Control mice exhibited exponential CRPC growth, whereas ENZ/LEU treatment delayed CRPC progression. PSAtk-VLPs/GCV significantly inhibited the growth of metastatic CRPC. However, no significant differences in survival were observed among the MOCK, ENZ/LEU, and PSAtk-VLP/GCV groups (log-rank test, p = 0.7351).Conclusion These findings support that JCPyV-derived virus-like particles constitute a promising therapeutic approach for metastatic CRPC, enabling systemic delivery of suicide gene therapy with selective inhibition of tumor growth and translational relevance.
SN - 2045-7634
ER -